peptide-yy and Hirschsprung-Disease

Enterocolitis (EC) remains the most serious complication of Hirschsprung's disease (HD). The aetiology of EC is uncertain. Ischemic and bacterial causes, and recently rotavirus infection, have been suggested to explain the occurrence of EC. The gut has an abundance of neuroendocrine (NE) cells which modulate gut function by endocrine, paracrine, or neurocrine routes. We studied NE cell populations in the bowel from 16 patients with HD (six of whom had clinical evidence of EC) and rectal tissue from 6 controls. Immunohistochemical studies were carried out using monoclonal and polyclonal antibodies against chromogranin A, synaptophysin (general markers of NE cells), 5-Hydroxytryptamine (5-HT), somatostatin, peptide YY (PYY), and glucagon/glicentin (neuropeptides). The six patients who had clinical evidence of EC prior to defunctioning colostomy showed histological evidence of EC in the defunctioned bowel. Using immunocytochemistry and serial tissue sectioning it was found that the number of NE cells in the aganglionic segment of colon in patients with HD was significantly (P < .05) increased compared with the numbers in the ganglionic segment. However, in the ganglionic colon, there was a significant (P < .05) reduction in NE cells in EC patients compared with non-EC patients. These results were seen both with the generic endocrine cell marker chromogranin A, which stains virtually all endocrine cells, and with specific markers for 5-HT, PYY, and glucagon/glicentin, which identify distinct subpopulations of endocrine cells. These differences may be partially responsible for previous conflicting reports of NE cell distribution in HD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Child; Child, Preschool; Chromogranin A; Chromogranins; Colon; Colostomy; Enterocolitis; Female; Glucagon; Hirschsprung Disease; Humans; Immunoenzyme Techniques; Infant; Male; Nerve Fibers; Neuropeptides; Peptide YY; Peptides; Serotonin; Somatostatin

The aganglionic intestine in Hirschsprung's disease displays a severe neuronal derangement. The changes are particularly evident in the muscular innervation. In the gut the endocrine cells are among the cells known to be influenced by neurons. We have, therefore, examined the endocrine cells in ganglionic and aganglionic intestine using immunocytochemistry and immunochemistry. The endocrine cells were studied using antibodies against the neuroendocrine marker chromogranin A, the amine serotonin and the hormonal peptides somatostatin, glucagon/glicentin and peptide YY (PYY), thus covering virtually all endocrine cell types known to occur in this region. The PYY concentration in the mucosal layer was measured by radioimmunoassay. In ganglionic as well as in aganglionic intestine large populations of cells storing chromogranin A, serotonin, glucagon and PYY and a smaller population of somatostatin cells were seen. There was an increase in the density of these cells in the aganglionic intestine compared with ganglionic. The data indicate that the endocrine cell populations in the intestinal wall can be maintained despite severe derangements of the nerve supply.

Topics: Cell Count; Chromogranin A; Chromogranins; Fluorescent Antibody Technique; Gastrointestinal Hormones; Glucagon; Hirschsprung Disease; Humans; Myenteric Plexus; Peptide YY; Peptides; Radioimmunoassay; Serotonin; Somatostatin